Fluoroalkene modification of mercaptoacetamide-based histone deacetylase inhibitors

Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. The mercaptoacetoamide-based inhibitors are reported to be less toxic than hydroxamate and are worthy of further consideration. Therefore, we have designed a series of analogs as potential inhibitors of HDACs, in which the mercaptoacetamide group was replaced by (mercaptomethyl)fluoroalkene, and their HDAC inhibitory activity was evaluated. Subnanomolar inhibition was observed for all synthetic compounds.     

Translocation of organic compounds in sunflower III. Effect of oligomycin, ouabain and phlorizin on translocation of sugars

The apical portions of intact sunflower leaves were infiltratedwith ¹⁴C-glucose, ¹⁴C-fructose or 3-O-methyl-¹⁴C-glucose andthe basal portions were treated with inhibitors. The effects of oligomycin, ouabain and phlorizin on translocationwere studied. Inhibition of translocation from the basal portionof the leaf to the stem was determined by experiments usingoligomycin. In other experiments, each leaf was divided intothree parts. The apical portion was fed with ¹⁴C-glucose andthe basal part treated with oligomycin. The effects of oligomycinon the distribution of ¹⁴C-glucose, ¹⁴C-sucrose, ¹⁴C-fructoseand ¹⁴C-sugar phosphate along the three parts of the leaf wereinvestigated. Inhibition of sucrose synthesis in the leavestreated with oligomycin was observed. Oligomycin inhibited ¹⁴Ctranslocation from the leaf. ¹Present address: Department of Biology, Faculty of Science,Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo,Japan. (Received August 17, 1978; )     

Selective excretion of anti-inflammatory cytokine Interleukin-10 in a superantigen-inducing neonatal infectious disease

Neonatal toxic shock syndrome (TSS)-like exanthematous disease (NTED) is an emerging neonatal infectious disease caused by TSS toxin-1 (TSST-1). Although NTED and TSS are caused by the same superantigenic exotoxin, NTED is less severe than TSS. The mechanism of this reduced severity in NTED has not been elucidated. Thirteen patients with NTED were enrolled in the study. We investigated serum cytokine profile using a cytometric bead array system with a cytokine panel. Expression of Vβ2 and CD45RO in CD4⁺ T cells was investigated in mononuclear cells by using flowcytometry. Ten patients with other bacterial infections and eight patients without any infections were also enrolled as control groups. The mean serum level of IL-10 was 1209.9 pg/mL in patients with NTED at the time of admission into the study. The other inhibitory cytokine, IL-4, exhibited a minimum level. The high level of IL-10 rapidly decreased within 3–9 days of the onset of NTED. The cytokine profile of NTED, with its high IL-10 level, was clearly different from that of the other bacterial infections. The increased level of IL-10 seems to be related to the reduced severity of NTED. Th2 shift is not thought to be the cause of this IL-10 excretion.     

Bio-inspired photoresponse of porphyrin-attached gold nanoparticles on a field-effect transistor

A bio-inspired photoresponse was engineered in porphyrin-attached Au nanoparticles (AuNPs) on a field-effect transistor (FET). The system mimics photosynthetic electron transfer, using porphyrin derivatives as photosensitizers and AuNPs as photoelectron counting devices. Porphyrin-protected AuNPs were immobilized onto the gate of an FET via the formation of self-assembled monolayers. Photoinduced electron transfer from the porphyrin led to single electron transfer at the Au nanoparticles, which was monitored via a changing gate voltage on the FET in the presence of organic electrolyte. The further attachment of other functional molecules to this system should enable various other potential functionalities. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: Keys to Produce Clean Energy.     

Cultured human corneal epithelial stem/progenitor cells derived from the corneal limbus

Stem/progenitor cells of the human corneal epithelium are present in the human corneal limbus, and several corneal epithelial stem/progenitor cell markers have been reported. Recently, the neurotrophin family receptors were reported to be useful markers of corneal epithelial stem/progenitor cells. Therefore, we examined an enzymatic separation method for obtaining corneal epithelial stem/progenitor cells and measuring the change in the expression of low-affinity neurotrophin receptor p75 (p75^NTR), a receptor belonging to the neurotrophin family. As a result, it was found that our separation method preserved cell viability. Furthermore, p75^NTR was mainly observed in epithelial basal cells as were the corneal epithelial stem/progenitor markers p63 and integrin β1. p75^NTR was also observed in the cultured cells, but its frequency decreased with passage. In conclusion, we propose that our culture method will enable the culture of corneal stem cells and that it is a useful tool for elucidating the molecular basis of the niche that is necessary for the maintenance of epithelial stem cells in the corneal limbus. Furthermore, we conclude that p75^NTR is a useful cell marker for evaluating the characteristics of stem/progenitor cells in culture.     

PCaPs,possible regulators of PtdInsP signals on plasma membrane

In plants, Ca²⁺, phosphatidylinositol phosphates (PtdInsPs) and inositol phosphates are major components of intracellular signaling. Several kinds of proteins and enzymes, such as calmodulin (CaM), protein kinase, protein phosphatase, and the Ca²⁺ channel, mediate the signaling. Two new Ca²⁺-binding proteins were identified from Arabidopsis thaliana and named PCaP1 and PCaP2 [plasma membrane (PM)-associated Ca²⁺(cation)-binding protein 1 and 2]. PCaP1 has an intrinsically disordered region in the central and C-terminal parts. The PCaP1 gene is expressed in most tissues and the PCaP2 gene is expressed predominantly in root hairs and pollen tubes. We recently demonstrated that these proteins are N-myristoylated, stably anchored in the PM, and are bound with phosphatidylinositol phosphates, especially PtdInsP₂s. Here we propose a model for the switching mechanism of Ca²⁺-signaling mediated by PtdInsPs. Ca²⁺ forms a complex with CaM (Ca²⁺-CaM) when there is an increase in the cytosol free Ca²⁺. The binding of PCaPs with Ca²⁺-CaM causes PCaPs to release PtdInsPs. Until the release of PtdInsPs, the signaling is kept in the resting state.Key words: calcium signal, calmodulin, inositol phosphate, intrinsically disordered protein, myristoylation, phosphatidylinositol phosphate, plasma membrane     

Increased Resistance to Cd(II) in the Primitive Red Algae Cyanidioschyzon merolae

Growth of Cyanidioschyzon merolae was inhibited depending on the cadmium(II) concentration in the culture medium. Although a lower level (0.01 mM) of Cd(II) inhibited growth by a factor of 0.5, higher levels (0.1 and 1 mM) induced lag periods of 10–14 days. Algal cells pretreated with 1 mM Cd(II) for 27 days grew steadily in 1 mM Cd(II) without the lag period, demonstrating that the cells became Cd(II) resistant (CdR). Cells remained resistant after four cycles (7 days per cycle) of washing and re-growing in medium without Cd(II), while intracellular Cd(II) decreased to undetectable levels. These results suggest that the Cd(II)-resistant phenotype is heritable. This phenomena may be attributable to the presence of genetic inhomogeneity in the wild-type cell populations or to mutagenesis caused by Cd(II) stress. Intracellular Cd(II) levels significantly decreased in the CdR phenotype compared to the wild-type cells, indicating that resistant cells may have a defective gene that codes for Cd(II)-uptake protein or the ability to secrete Cd(II).     

Electroencephalogram abnormalities in panic disorder patients: a study of symptom characteristics and pathology

Background  

Since the 1980s, a high EEG abnormality rate has been reported for patients with panic disorder. However, how the EEG abnormalities of panic disorder patients are related to the clinical features and pathology of these patients has yet to be clarified. In this study we investigated whether or not EEG abnormalities are related to the 13 symptoms in the DSM-IV criteria for a diagnosis of panic attacks.     

DNA polymerase D temporarily connects primase to the CMG-like helicase before interacting with proliferating cell nuclear antigen

The eukaryotic replisome is comprised of three family-B DNA polymerases (Polα, δ and ϵ). Polα forms a stable complex with primase to synthesize short RNA-DNA primers, which are subsequently elongated by Polδ and Polϵ in concert with proliferating cell nuclear antigen (PCNA). In some species of archaea, family-D DNA polymerase (PolD) is the only DNA polymerase essential for cell viability, raising the question of how it alone conducts the bulk of DNA synthesis. We used a hyperthermophilic archaeon, Thermococcus kodakarensis, to demonstrate that PolD connects primase to the archaeal replisome before interacting with PCNA. Whereas PolD stably connects primase to GINS, a component of CMG helicase, cryo-EM analysis indicated a highly flexible PolD–primase complex. A conserved hydrophobic motif at the C-terminus of the DP2 subunit of PolD, a PIP (PCNA-Interacting Peptide) motif, was critical for the interaction with primase. The dissociation of primase was induced by DNA-dependent binding of PCNA to PolD. Point mutations in the alternative PIP-motif of DP2 abrogated the molecular switching that converts the archaeal replicase from de novo to processive synthesis mode.